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Lee Hood, President and Co-founder Institute for Systems Biology, Seattle

Senior Vice President and Chief Science Officer Providence St. Joseph Health Oct. 14, 2016

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Conflict of interest statement—showing how start ups are essential for democratization of technologies and strategies and building and enabling visions

•! Arivale—a scientific wellness company directed at consumers •! Applied Biosystems—commercialization of 1st 4 Hood instruments •! Rosetta—computational approaches to deciphering the complexity of

biology—ink jet technology--ultimately to Agilent •! Nanostring—single RNA molecule analysis—now DNA and protein

analyses as well •! Integrated Diagnostics—blood protein diagnostics company

employing targeted proteomics •! Indi Molecular—a company developing peptide-based, protein-capture

agents for in vitro and in vivo diagnostics and as well as targeted therapeutics—will replace monoclonal antibodies in 10-15 years

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Scientific Wellness:

Dense, dynamic

personal data clouds

/%

Bringing P4 medicine to

Providence St. Joseph Health

and the US Healthcare

System

012.%

I Participated in Seven Paradigm Changes in Biology Dealing with Complexity and

Creating the Background for ISB

2Brought engineering to biology 23/1%

0%The Human Genome Project 4%

Cross-disciplinary biology

5Systems biology

Systems medicine/ Emergence of proactive P4 medicine

6

Six Instruments Developed by Hood Laboratories

1! Protein Sequencer Caltech—Applied Biosystems

2! Protein Synthesizer Caltech—Applied Biosystems

3! DNA Sequencer Caltech—Applied Biosystems

4! DNA Synthesizer Caltech—Applied Biosystems

5! Ink-jet oligonucleotide DNA synthesizer MBT/UW--Rosetta then Agilent

6! Nanostring nCounter ISB--Nanostring

2%Brought engineering to biology

23/1%

Predictive Preventive Personalized Participatory

60#/+)%+39%/-(%+GBHI+@-7)1)$-J+

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These data clouds are the essence of Precision Medicine

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Vision – Clearly articulated systems and P4 medicine

2006

Tipping point – Luxembourg partnership--$100 million over 5 years for P4 technology and strategies

2008

P4 pilot program –Systems(P4) medicine pilot 100,000 person wellness project proposed—108 person wellness project 2014

2012

Precision medicine – Obama’s Precision Medicine Initiative: dense, dynamic, personalized data clouds 2015

P4 medicine to patients– Affiliation between ISB and Providence St. Joseph Health to bring P4 medicine to patients

2016

2006

2008

2012

2015

2016

7%

“The tipping point is that magic moment when an idea, trend, or social behavior crosses a threshold, tips, and spreads like wildfire.”

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S3?+39%/-(%R7")D-$+M'D-.+#$7+A(-"*)$*+!-10$'.'*)-%+3rd generation DNA sequencing—Lausted, Hood Northwest Bio •! L(&;E;<+M&(&;HC(&&+)N%JI&-)+%*;)+H')+N%+)+H?<;&IH%B+?+H,;&%%

Diagnostic microfluidics and nanotechnology—Demitrov, Lausted, Hood, Heath—Nanostring •! "I&-)+%*;)+H')+%&'H)+IH%(HIB%(&()@J+JN%JI&-)+KH+))%(&()@J+JN%E<;?+I&%(&()@J+J%

Peptide protein-capture agents—Heath, Hood Indi Molecular •! O;<%I&%DI?<;%(&B%I&%DID;%BI(-&;J,HJ%(&B%(J%%B<'-J%?;%<+E)(H+%(&,:;BI+J%

Crosslinking proteins--Ranish To determine molecular machine structure and network structures

Global mass spectrometry—Moritz, Aebersold •! P<;?+;*+%(&()@J+J%Q"!$R#ST.111%E<;?+I&J%F<;*%:);;B%%

Targeted mass spectrometry (SRM)—Moritz, Aebersold, Hood •! $&()@A+%211%E<;?+I&J%F<;*%H;*E)+9%J(*E)+J%)IU+%:);;B%

High throughput biological assays—Aitchison, Tyers

Single-cell highly multiplexed omic and phenotypic analyses—Huang, Trachana, Bargaje, Sheldon V+?+H,&-%W'(&,A+B%H+))%E;E')(,;&J%(&B%,EEI&-%E;I&?J%

ISB Systems-driven strategies are transforming healthcare

•! Family genome sequencing—identifying disease genes—Glusman, Roach, Hood –! Identify disease, wellness genes and drug-intolerant genes. For the identification for each individual’s more than

1000 or more actionable genes •! Follow disease progression from beginning to end in model organisms—delineating the

dynamical disease-perturbed networks—Hood, Chen, Bargaje, Inyoul Lee –! Enable mechanistic insights, diagnosis, therapy and prevention for the individual patient

Transform blood into a window to distinguish health from disease with mass spectrometry—Moritz, Kearney, Hood, Price, Integrated Diagnostics Disease diagnostics, assess drug toxicity, assess wellness –! Human examples: lung cancer, PTSD, liver toxicity, liver hepatitis, preterm birth

•! Dense, dynamic, personal data clouds to study wellness, wellness to disease transitions and disease progression—N=1 experiments—Hood and Price, Arivale

•! Stratify diseases and patients into their distinct subtypes—Hood and Price –! For impedance match with appropriate drugs –! Human example: various cancers

•! Enable a new systems-driven computational approaches to pioneering drug reuse and drug target discovery—Baliga, Shmulevich, Price

•! Re-engineer disease-perturbed networks to normalcy with drugs, Repurpose drugs. faster and cheaper, drugs that prevent networks from becoming disease-perturbed

•! Creating billions of chemical entities to identify new drugs through very high throughput screening—Tyers Newco

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•! Individual •! Population

•! Wellness & disease •! Only disease

•! Patient activated social networks

•! Personalized data clouds

•! Averaged patient populations

•! Personalized data clouds for clinical trials (N=1 experiments)

•! Averaged patient populations for clinical trials

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Imprecision Medicine: Time for N=1 Drug Trials to Stratify Disease Subtypes

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Dense, dynamic, personal data clouds will enable us to: •! Optimize human potential / wellness •! Identify earliest wellness to disease transitions—reverse preventive med. 21st cent. •! Follow disease, response to therapy and return to health (follow high risk individuals) •! N=1 experiments—from large numbers aggregation of similar patients

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More than half of all children born today in developed countries can expect to celebrate their 100th birthday.

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!0-+XQd+B-"%'$++6-..$-%%+B"'h-1/++PQXH+G,B6BI+Principal Investigators: Lee Hood and Nathan Price Using dense, dynamic, personal data clouds for wellness IRB approved study

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Database of actionable

possibilities that will grow over

time

GENOME

Whole Genome Sequencing SNPs Millions

LABS

Detailed lab tests 3x (blood, urine, saliva) Clinical chem. 150

Metabolites 1700 Proteins 400

Continual self-tracking & lifestyle monitoring

MICROBIOME

Gut Microbiome 3x

Creating dense, dynamic, personal data clouds

SELF-TRACKING%

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Sandi Kaplan, MS, RD Craig Keebler, MD

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Correlations between all of our five data quadrants for

108 individuals

Determination of genetic risk and correlation with disease phenotype

State transitions: For wellness and

disease states

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Multi-omic Correlation Network –!We identified more than 4000

statistically significant correlations between six data types.

–!Among the top correlations are existing disease treatments for cholesterol and diabetes patients, that we independently observed.

We identify ‘communities’ in the correlation network – sets of analytes that are more connected with each other than with the rest of the network.

Substructures of the Correlation Network

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Individuals contain different subsets of the 59 GWAS variants that affect cholesterol levels

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LDL cholesterol in Participants Shows Monotonic Relationship with ‘Genetic Risk’

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GWAS Variants Have Been Determined for About 60 Diseases and Traits

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State Transitions: Wellness and Disease

•! Wellness to greater wellness—metrics for wellness

•! Wellness to earliest disease transitions for all common diseases—learning how to achieve early reversal will be the preventive medicine of the future

•! Disease progression to therapy (to wellness)—powerful disease stratification and identification of effective therapies

•! Transitions due to the individual acting upon actionable possibilities—enormous positive reinforcement

HPWP Initial Clinical Labs Discovery: High Rate of Actionable Clinical Lab Results

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Lifestyle: Genetics and environment

•! Genetics of diet •! Genetics of exercise •! Genetics of athletic injuries •! Nutrition •! Inflammation •! Heavy metal toxicity

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I can take control of my health with the proper data/coaching.

Your genome does not control your destiny – just your potential.

We are less well than we think. Everyone has multiple actionable possibilities.

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W")D#.-%•! A consumer-oriented

scientific wellness company

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Arivale: Six Health Dimensions

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•! Research to validate wellness metrics

•! Research for better assays

•! Improve wellness analytics

•! Optimize wellness

•! Study wellness to disease transitions

•! Study disease [progression, response to therapy and transition to wellness

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B"'D)7-$1-+3/T+m'%-<0+,-#./0RS3?+Wn.)#4'$+ISB is the research arm of Providence LH is SVP and chief science officer of Providence Initiating Four Translational Pillars—bringing P4 medicine to patients

Alaska, California, Idaho, Oregon, Washington, New Mexico, Texas

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Intersecting the clinical data with the dense, dynamic data clouds: powerful strategic partnership

•! Data mining for hypothesis generation •! Most promising need to be tested experimentally •! Clinical trials •! Learning healthcare system – working research in-line where appropriate

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